Abstract Psilocybin is a serotonergic psychedelic drug with emerging therapeutic applications, yet its actions under glutamatergic dysfunction, and relevance to schizophrenia and associated psychiatric disorders, remain unclear. We examined the acute and long-lasting effects of psilocybin (1 mg/kg, intraperitoneal) on behavioral and neural outcomes in the metabotropic glutamate receptor 5...
Zenodo (CERN European Organization for Nuclear Research)July 17, 2026Bartosz Niciński, Magdalena Kloc, Ewa Wiench, Natasza Millan, Aleksandra Blicharz, Wojciech Kozdraś, Lidia Kozaczko, Gabriela Szewczyk, Elżbieta Bukowczan, Alicja Zając, Damian Broda, Alicja Benecka
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Major depressive disorder is a highly burdensome psychiatric condition worldwide, and many patients do not achieve full remission after standard monoaminergic antidepressant treatment. This has contributed to growing interest in rapid-acting antidepressant interventionstargeting neurobiological pathways beyond traditional serotonin, norepinephrine, and dopamine mechanisms. This review...
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a neural stem cell-derived in vitro...
Classic psychedelics, including psilocybin, LSD, DMT, 5-MeO-DMT, mescaline, and phenethylamines such as DOI, exert their core effects through 5-HT2A receptor agonism, inducing widespread neurobiological and behavioral changes relevant to psychiatric research. Emerging evidence suggests that these effects are modulated by sex, yet this dimension remains underrepresented in studies. This review...
New psychoactive substances (NPSs) often emerge on the illicit drug market with limited pharmacological or toxicological data. Synthetic cathinones are the second largest NPS group, often mimicking the effects of classical stimulants such as cocaine and methylenedioxymethamphetamine (MDMA). Such stimulants primarily target dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters,...
A resurgent therapeutic frontier, the contemporary renaissance in psychedelic science has accelerated investigation of classic serotonergic psychedelics (psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline), empathogenic entactogenic agents (3,4-methylenedioxymethamphetamine (MDMA)), and glutamatergic dissociatives (ketamine) as adjuncts to psychotherapy. While...
High Resolution Image Download MS PowerPoint Slide The psychedelic therapeutics field continues to evolve beyond classical hallucinogens toward integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications disclose selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds,...
European Journal of PharmacologyJuly 10, 2026Amanda Gollo Bertollo, Vinicius Alexandre Wippel, Maiqueli Eduarda Dama Mingoti et al.
Major Depressive Disorder (MDD) is a debilitating mental health condition that significantly impacts quality of life. Despite available pharmacological treatments, response rates remain suboptimal, with a considerable number of patients experiencing treatment-resistant depression (TRD). Indeed, classical antidepressants, primarily targeting monoaminergic systems, exhibit a therapeutic delay due...
In recent years, psychedelics have shown promising results as therapeutic interventions for individuals with depression, terminal illnesses, substance use disorder, neurodegenerative diseases, trauma and obsessive-compulsive disorder. Moreover, research involving psychedelics have contributed to the understanding of the neurobiological mechanisms behind the "psychedelic state of consciousness"...
Open Science FrameworkJuly 9, 2026Raul Edison Luna Lazo, Nicole Milagritos Cardoso Azorza, Jatziri Yanina Vilca Yanac et al.
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Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric condition characterized by intrusive thoughts and repetitive behaviors that cause distress and functional impairment worldwide. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy are first-line treatments, a considerable proportion of patients show an insufficient response, supporting the need for...
The serotonin 1B receptor can be studied in vivo with PET using [^11C]AZ10419369, and has been linked to both the pathophysiology and treatment of major depressive disorder (MDD). Ketamine and electroconvulsive therapy (ECT) both exert rapid and potent antidepressive effects, and although these treatments may not act directly on the serotonin system, they both cause dose-dependent increases in...
There is limited or indirect evidence suggesting that combined use of MDMA and SSRIs may increase the risk of serotonin syndrome. Healthcare providers should be vigilant in identifying symptoms and discourage such drug interactions.
Molecular PsychiatryJuly 7, 2026Axel F. Rosado, Abigail L. Yu, Jen-Hau Yang et al.
Classic serotonergic psychedelics such as psilocybin act as agonists at cortical serotonin (5-HT) 2A receptors (5-HT 2A R), inducing psychedelic effects in humans and head-twitch responses (HTRs) in rodents. Another class of psychedelic drugs called entactogens, exemplified by MDMA, function primarily as monoamine releasers and typically evoke minimal HTR despite causing serotonin release. The...
Background/Objectives: Psilocibin (PSY), a serotonergic hallucinogen, has attracted increasing scientific interest due to its therapeutic potential, particularly in treatment-resistant depression. In parallel with its growing clinical and research relevance, important questions have emerged regarding its safety profile, including potential effects on the liver, kidneys, cardiovascular system,...
The Psilocybe cubensis mushroom is recognized as the primary source of psilocybin in the Americas, occurring naturally across various regions. This fungus has a long history of use in Mesoamerican rituals due to its capacity to induce altered states of consciousness. The defining characteristic of Psilocybe mushrooms is their psilocybin content. Following ingestion, psilocybin is metabolized...
High Resolution Image Download MS PowerPoint Slide Provided herein are novel 6,5-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse, and headaches, and processes for preparing such compounds.
Abstract Serotonin (5-HT) 2A receptors (5-HT 2 AR) modulate corticolimbic circuits regulating fear extinction. Although activation of these receptors has been shown to facilitate fear extinction, the behavioral consequences of 5-HT 2 AR antagonism during extinction is not well defined. Here, we examined the systemic effects of two 5-HT 2 A receptor antagonists, the mixed 5-HT 2 A/ 2 C...
Classical serotonergic psychedelics primarily exert their profound effects through agonism at the serotonin 2A (5-HT2A) receptor, which is abundantly expressed in many cortical regions, particularly in layer V pyramidal neurons of associative and visual areas. At the cellular level, these receptors are predominantly localized postsynaptically on the soma and apical dendrites. This review...
Fear-related psychiatric disorders such as phobias and anxiety are insufficiently treated by current therapies. Psychedelics targeting 5-HT₂A receptors show promise in modulating fear circuits, but their specific neurobiological substrates remain unclear. This study investigates the effects of 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), a psychedelic compound, on innate fear responses and...
BackgroundAlcohol use disorder (AUD) remains difficult to treat with lasting success, leading to growing interest in alternative therapeutic approaches. Psychedelic compounds such as Ayahuasca, a traditional brew used in Indigenous Amazonian ceremonies containing N,N-dimethyltryptamine (DMT) along with monoamine oxidase-inhibiting β-carbolines, have shown promise in reducing addictive...